Synthesis and Inhibitory Activity towards Monoamine Oxidase A and B of 8‐Functionalized 3‐Fluoro‐2‐methyl‐benzo[4,5]thiazolo[3,2‐a]pyrimidin‐4‐ones

Abstract

8‐Chloro‐3‐fluoro‐2‐methyl‐benzo[4,5]thiazolo[3,2‐a]pyrimidin‐4‐one was synthesized and employed in various palladium catalysed cross‐coupling‐reactions, including Suzuki‐Miyaura, Sonogashira and Buchwald‐Hartwig reactions, delivering 8‐aryl‐, 8‐alkynyl‐ and 8‐amino‐3‐fluoro‐2‐methyl‐benzo[4,5]thiazolo[3,2‐a]pyrimidin‐4‐ones in good to excellent yields. The synthesized derivatives were analysed for their monoamine oxidase (MAO−A and MAO−B) inhibitory potential. Most of the compounds exhibited moderate to good inhibitory activity towards MAO−A and/or MAO−B. Docking analysis was performed to verify the experimental results. Hence, 8‐substituted‐3‐fluoro‐2‐methyl‐benzo[4,5]thiazolo[3,2‐a]pyrimidin‐4‐ones might be potential lead compounds towards novel monoamine oxidase inhibitors.

Synthesis of 2‐Alkynyl‐ and2‐Amino‐12H‐benzothiazolo[2,3‐b]quinazolin‐12‐ones and Their Inhibitory Potential against Monoamine Oxidase A and B

“…Among all evaluated compounds, 4 h was found as the most potent and selective inhibitor of MAO−A with an IC 50 ± SEM value of 0.42 ± 0.01 μM, followed by 4 g and 4 e showing strong inhibition values of 1.04 ± 0.06 and 4.01 ± 0.22 μM, respectively. Compound 4 h proved to be considerably more active against MAO−A than the best derivative of our recently reported 2‐aryl‐12 H ‐benzothiazolo[2,3‐ b ]quinazolin‐12‐one series (2.82 μM) …”

“…Substitution with 3‐trifluoromethylbenzylamine 4 e is noticed as a potent inhibitor for both isoforms with slightly reduced inhibitory activity towards MAO−A. Analogously, in our previous study on corresponding 2‐aryl‐12 H ‐benzothiazolo[2,3‐ b ]quinazolin‐12‐ones, compounds substituted by fluorinated aryl moieties were identified as the most potent inhibitors among the tested derivatives . Hence, these results indicate a positive impact of aryl fluoride substituents on the inhibitory activity of 12 H ‐benzothiazolo[2,3‐ b ]quinazolin‐12‐ones.…”

“…Recently, we have reported the synthesis of 8‐functionalized‐2‐methyl‐3‐fluoro‐benzo[4,5]thiazolo[3,2‐ a ]pyrimidin‐4‐ones as well as the synthesis of 2‐arylated benzothiazoloquinazolinones and investigated their potential as MAO inhibitors . For the latter compounds we observed good inhibition concentrations for MAO−A and MAO−B which suggested that the benzothiazolo[2,3‐ b ]quinazolin‐12‐one core structure is quite promising as a scaffold for further investigations and SAR studies.…”

MgO nanopowders catalyzed synthesis of pyrano[4,3‐d]thiazolo[3,2‐a]pyrimidine derivatives

“…[8,9] Benzo [4,5]thiazolo[3,2-a] pyrimidin-4-ones exhibit good inhibitory activity towards monoamine oxidase. [10] Therefore, the synthesis of thiazolo[3,2-a]pyrimidines has attracted wide attention of the chemical researchers.…”